Early alveolar macrophage response and IL-1R-dependent T cell priming determine transmissibility of Mycobacterium tuberculosis strains.

Mechanisms underlying variability in transmission of Mycobacterium tuberculosis strains remain undefined. By characterizing high and low transmission strains of M.tuberculosis in mice, we show here that high transmission M.tuberculosis strain induce rapid IL-1R-dependent alveolar macrophage migration from the alveolar space into the interstitium and that this action is key to subsequent temporal events of early dissemination of bacteria to the lymph nodes, Th1 priming, granulomatous response and bacterial control. In contrast, IL-1R-dependent alveolar macrophage migration and early dissemination of bacteria to lymph nodes is significantly impeded in infection with low transmission M.tuberculosis strain; these events promote the development of Th17 immunity, fostering neutrophilic inflammation and increased bacterial replication. Our results suggest that by inducing granulomas with the potential to develop into cavitary lesions that aids bacterial escape into the airways, high transmission M.tuberculosis strain is poised for greater transmissibility. These findings implicate bacterial heterogeneity as an important modifier of TB disease manifestations and transmission.

Molecular Epidemiology of Mycobacterium tuberculosis strains isolated from pulmonary tuberculosis patients in south Ethiopia.

INTRODUCTION: Understanding the epidemiology of tuberculosis is limited by lack of genotyping data. We sought to characterize the drug susceptibility testing patterns and genetic diversity of M. tuberculosis isolates in southern Ethiopia. METHODOLOGY: A cross-sectional study was conducted among newly diagnosed sputum smear positive patients with tuberculosis visiting nine health facilities in southern Ethiopia from June 2015 to May 2016. Three consecutive sputum samples (spot-morning-spot) per patient were examined using acid-fast bacilli smear microscopy with all smear positive specimens having acid-fast bacilli cultures performed. M. tuberculosis isolates had drug susceptibility testing performed using indirect proportion method and were genotyped with RD9 deletion analysis and spoligotyping. Mapping of strain was made using geographic information system. RESULTS: Among 250 newly diagnosed patients with tuberculosis, 4% were HIV co-infected. All 230 isolates tested were M. tuberculosis strains belonging to three lineages: Euro-American, 187 (81%), East-African-Indian, 31 (14%), and Lineage 7 (Ethiopian lineage), 8 (4%); categorized into 63 different spoligotype patterns, of which 85% fell into 28 clusters. M. tuberculosis strains were clustered by geographic localities. The dominant spoligotypes were SIT149 (21%) and SIT53 (19%). Drug susceptibility testing found that 14% of isolates tested were resistant to > 1 first line anti- tuberculosis drugs and 11% to INH. SIT 149 was dominant among drug resistant isolates. CONCLUSIONS: The study revealed several clusters and drug resistant strains of M. tuberculosis in the study area, suggesting recent transmission including of drug resistant tuberculosis. Wider monitoring of drug susceptibility testing and geospatial analysis of transmission trends is required to control tuberculosis in southern Ethiopia.

Knowledge and perception of treatment among tuberculosis patients attending primary care clinics in Malaysia.

INTRODUCTION: Tuberculosis is a disease of public health concern. It can be treated effectively with good knowledge about the disease and complete adherence to the recommended treatment regime. This study is intended to assess the level of knowledge and perception of treatment among tuberculosis patients attending primary care clinics. METHODOLOGY: We conducted a cross-sectional study using a validated self-administered questionnaire among tuberculosis patients attending primary care clinics in Johor Bahru district. A total of 208 tuberculosis patients were enrolled in this study through convenience sampling. We assessed the general knowledge, transmission, causes, and prevention of tuberculosis, where higher scores indicated better knowledge. For the perception of treatment, a higher mean score indicated a more negative perception. RESULTS: The mean score for knowledge on tuberculosis was 54.33 ± 12.78, ranging from 25 to 88.9%. The mean score for perception was 2.75±0.52, ranging from 2.15-3.39. We found that although 88.9% of respondents knew a person could be infected with TB through inhalation of tuberculosis bacilli, a majority believed that smoking (68.2%), sharing food (69.2%), and eating from the same plate (66.8%) are causes of tuberculosis. Moreover, there was still a negative perception regarding the treatment of tuberculosis with the highest mean score for the statement 'I am afraid if I am told I am tuberculosis positive'. CONCLUSIONS: We found that there were gaps in knowledge among tuberculosis patients. Intermittent counseling during the treatment re-enforces the knowledge of tuberculosis. An updated standardized counseling sheet of tuberculosis Health Education should be included along with staff training to update their knowledge as part of their important role in health education in tuberculosis prevention.

Predictors of delayed sputum smear conversion among pulmonary tuberculosis patients in Kota Kinabalu, Malaysia: A retrospective cohort study.

ABSTRACT: Smear-positive pulmonary tuberculosis (SPPTB) is the major contributor to the spread of tuberculosis (TB) infection, and it creates high morbidity and mortality worldwide. The objective of this study was to determine the predictors of delayed sputum smear conversion at the end of the intensive phase of TB treatment in Kota Kinabalu, Malaysia.This retrospective study was conducted utilising data of SPPTB patients treated in 5 TB treatment centres located in Kota Kinabalu, Malaysia from 2013 to 2018. Pulmonary TB (PTB) patients included in the study were those who had at least completed the intensive phase of anti-TB treatment with sputum smear results at the end of the 2nd month of treatment. The factors associated with delayed sputum smear conversion were analyzed using multiple logistic regression analysis. Predictors of sputum smear conversion at the end of intensive phase were evaluated.A total of 2641 patients from the 2013 to 2018 periods were included in this study. One hundred eighty nine (7.2%) patients were identified as having delayed sputum smear conversion at the end of the intensive phase treatment. Factors of moderate (advanced odd ratio [aOR]: 1.7) and advanced (aOR: 2.7) chest X-ray findings at diagnosis, age range of >60 (aOR: 2.1), year of enrolment 2016 (aOR: 2.8), 2017 (aOR: 3.9), and 2018 (aOR: 2.8), smokers (aOR: 1.5), no directly observed treatment short-course (DOTS) supervisor (aOR: 6.9), non-Malaysian citizens (aOR: 1.5), and suburban home locations (aOR: 1.6) were associated with delayed sputum smear conversion at the end of the intensive phase of the treatment.To improve sputum smear conversion success rate, the early detection of PTB cases has to be fine-tuned so as to reduce late or severe case presentation during diagnosis. Efforts must also be in place to encourage PTB patients to quit smoking. The percentage of patients assigned with DOTS supervisors should be increased while at the same time ensuring that vulnerable groups such as those residing in suburban localities, the elderly and migrant TB patients are provided with proper follow-up treatment and management.

Extending contact screening within a 50-m radius of an index tuberculosis patient using Xpert MTB/RIF in urban Pakistan: Did it impact treatment outcomes?

BACKGROUND: Pakistan implemented initiatives to detect tuberculosis (TB) patients through extended contact screening (ECS); it improved case detection but treatment outcomes need assessment. OBJECTIVES: To compare treatment outcomes of pulmonary TB (PTB) patients detected by ECS with those detected by routine passive case finding (PCF). METHODS: A cohort study using secondary program data conducted in Lahore, Faisalabad and Rawalpindi districts and Islamabad in 2013-15. We used log binomial regression models to assess if ECS was associated with unfavorable treatment outcomes (death, loss-to-follow-up, failure, not evaluated) after adjusting for potential confounders. RESULTS: We included 79,431 people with PTB; 4604 (5.8%) were detected by ECS with 4052 (88%) bacteriologically confirmed. In all PTB patients the proportion with unfavorable outcomes was not significantly different in ECS group (9.6%) compared to PCF (9.9%), however, among bacteriologically confirmed patients unfavorable outcomes were significantly lower in ECS (9.9%) than PCF group (11.6%, P = 0.001). ECS was associated with a lower risk of unfavorable outcomes (adjusted relative risk (aRR) 0.90; 95% CI 0.82-0.99) among 'all PTB' patients and bacteriologically confirmed PTB patients (aRR 0.91; 95% CI 0.82-1.00). CONCLUSION: In PTB patients detected by ECS the treatment outcomes were not inferior to those detected by PCF.

Cough-independent production of viable Mycobacterium tuberculosis in bioaerosol.

BACKGROUND: Symptoms of infectious respiratory illnesses are often assumed to drive transmission. However, production and release of Mycobacterium tuberculosis (Mtb) bioaerosols is poorly understood. We report quantitation of Mtb exhaled during specific respiratory manoeuvres. METHODS: Direct capture of nascent bioaerosol particles and indirect collection of aged particles was performed in 10 healthy subjects. Indirect and direct capture of exhaled viable Mtb bacilli was compared in 38 PTB patients and directly captured viable Mtb during cough and bronchiole-burst manoeuvres in 27 of the PTB patients. RESULTS: Direct sampling of healthy subjects captured larger bioaerosol volumes with higher proportions of 2-5 µm particles than indirect sampling. Indirect sampling identified viable Mtb in 92.1% (35 of 38) of PTB patients during 60-min relaxed breathing, median bacillary count 7.5 (IQR: 3.25-19). Direct sampling for 10-min identified Mtb in 97.4% (37 of 38) of PTB patients with higher bacilli counts (p < 0.001), median 24.5 (IQR:11.25-37.5). A short 5-min sampling regimen of 10 coughs or 10 bronchiole-burst manoeuvres yielded a median of 11 (IQR: 4-17) and 11 (IQR: 7-17.5) Mtb bacilli, respectively (p = 0.53). CONCLUSIONS: Peripheral lung bioaerosol released through deep exhalations alone contained viable Mtb suggesting non-cough transmission is possible in PTB.

Transmission analysis of a large tuberculosis outbreak in London: a mathematical modelling study using genomic data.

Outbreaks of tuberculosis (TB) - such as the large isoniazid-resistant outbreak centred on London, UK, which originated in 1995 - provide excellent opportunities to model transmission of this devastating disease. Transmission chains for TB are notoriously difficult to ascertain, but mathematical modelling approaches, combined with whole-genome sequencing data, have strong potential to contribute to transmission analyses. Using such data, we aimed to reconstruct transmission histories for the outbreak using a Bayesian approach, and to use machine-learning techniques with patient-level data to identify the key covariates associated with transmission. By using our transmission reconstruction method that accounts for phylogenetic uncertainty, we are able to identify 21 transmission events with reasonable confidence, 9 of which have zero SNP distance, and a maximum distance of 3. Patient age, alcohol abuse and history of homelessness were found to be the most important predictors of being credible TB transmitters.

Estimating Cost Functions for Resource Allocation Using Transmission Models: A Case Study of Tuberculosis Case Finding in South Africa.

OBJECTIVE: Cost functions linked to transmission dynamic models are commonly used to estimate the resources required for infectious disease policies. We present a conceptual and empirical approach for estimating these functions, allowing for nonconstant marginal costs. We aim to expand on the current approach which commonly assumes linearity of cost over scale. METHODS: We propose a theoretical framework adapted from the field of transport economics. We specify joint functions of production of services within a disease-specific program. We expand these functions to include qualitative insights of program expansion patterns. We present the difference in incremental total costs between an approach assuming constant unit costs and alternative approaches that assume economies of scale, scope and homogeneous or heterogeneous facility recruitment into the programme during scale-up. We illustrate the framework's application in tuberculosis, using secondary data from the literature and routine reporting systems in South Africa. RESULTS: Economies of capacity and scope substantially change cost estimates over time. Cost data requirements for the proposed approach included standardized and disaggregated unit costs (for a limited number of outputs) and information on the facilities network available to the program. CONCLUSIONS: The defined functional form will determine the magnitude and shape of costs when outputs and coverage are increasing. This in turn will impact resource allocation decisions. Infectious diseases modelers and economists should use transparent and empirically based cost models for analyses that inform resource allocation decisions. This framework describes a general approach for developing these models.

Latent tuberculosis among household contacts of pulmonary tuberculosis cases in Nairobi, Kenya.

INTRODUCTION: Household Contacts (HHCs) of Pulmonary Tuberculosis (PTB) patients have a higher risk of latent tuberculosis infection (LTBI). However, its prevalence and risk factors among adults living with PTB patients are poorly documented in Kenya. OBJECTIVE: to determine the prevalence and risk factors for LTBI among adult HHCs of PTB patients in Kenya. METHODS: this was an analytical cross-sectional study of HHCs of PTB patients in Nairobi, Kenya. Socio-demographic data was captured on questionnaires and blood samples drawn for Interferon gamma (IFN-γ) quantification. Univariate and multivariate analyses using the Statistical Package for Social Scientists (SPSS) was used to determine the prevalence of LTBI and risk factors at 95% Confidence Interval (CI). RESULTS: a total of 166 PTB patients yielded 175 HHCs of whom 29.7% (52/125) were males and 70.3% (123/125) were females. A majority of HHCs [65.7% (115/175)] lived in a single-room house with the patient and [37.7% (66/175)] were in the age group 30-39-years. The overall prevalence of LTBI was 55.7%, peaking among spouses of the patients [70.0% (14/20) and the 30-39 year age group [63.5% (42/66)]. Potential risk factors for LTBI included cohabiting with a PTB patient for 8 to 12 weeks [OR = 3.6 (0.70-18.5), p = 0.107], being a spouse of the patient [OR = 2.0 (0.72-5.47), p = 0.173] and sharing a single room with the patient [OR = 1.58 (0.84 - 2.97), p = 0.158]. CONCLUSION: the high prevalence of LTBI among adult HHCs of PTB patients in this population demonstrates the need for targeted contact-screening programs in high TB transmission settings.

Tuberculosis screening in household contacts of pulmonary tuberculosis patients in an urban setting.

BACKGROUND: Household contacts (HHC) of tuberculosis (TB) patients are at risk of TB infection and disease. The study assessed the utility of "Household contact card and register" for screening of HHC of pulmonary TB (PTB) patients for TB and explored the reasons for HHC not being screened and followed-up. METHODS: The "Household contact card and register" was implemented by the Health Care Workers (HCW) of the TB Control Programme in Chennai District for screening HHC of index PTB patients initiated on treatment between June and August, 2018. Contacts were required to be screened within 2 months of treatment initiation of the index patient. Details collected included age, gender, smoking, alcohol use, immunosuppressive conditions and TB treatment. Symptom screening along with chest radiograph and or sputum examination was attempted. Follow-up TB screening at 6 and 12 months were performed. Screening of HHC was compared pre and post implementation phase. Proportions were computed for the data analysed. RESULTS: HHC information was documented for 93% (1268/1364) of Index PTB patients. The main reasons of non-listing of HHC in 96 PTB patients were HCW non-availability or non-co-operation of the HHC. There were 2150 (80%) contacts who were screened for TB. Inconvenient time, feeling healthy, stigma, out-station visit were the main reasons for 537 contacts not undergoing TB screening. Anti-TB treatment was initiated in 21 (1%) of contacts diagnosed with TB. Preventive therapy was initiated in 59% (81/138) of contacts aged <6 years. The screening of HHC improved from 36% to 80% during the implementation phase. Follow-up TB screening at 12 months was performed in 50% of HHC and 2 incident TB cases were identified. CONCLUSION: "Household contact card and register" is a useful tool for HCWs for TB screening in HHC of PTB patients. Reasons for non-adherence to contact screening needs to be addressed.

Prevalence of LTBI among household contacts of sputum positive TB patients receiving DOTS chemotherapy.

OBJECTIVES: 1. To estimate the prevalence of latent tuberculosis infection among household contacts of sputum positive pulmonary tuberculosis patient receiving DOTS chemotherapy. 2. To evaluate the risk factors among household contacts of sputum positive pulmonary tuberculosis patient receiving DOTS chemotherapy. 3. To evaluate the degree of exposure among household contacts of sputum positive pulmonary tuberculosis patient receiving DOTS chemotherapy. METHODS: This study was a cross sectional done among 220 household contacts of age 12 years and above (male and female) of the index sputum positive patients receiving DOTS. Mantoux skin test (Tuberculin Skin Test - TST) was administered by the principal investigator along with TST reading & final diagnosis. Chi-square test was done to find out the association. RESULTS: Out of 220 household contacts tested, 43.6% (96) tested positive for latent TB (induration ≥10mm) with 95% CI ranging from 37% to 50%. The prevalence of latent TB among men and women are 35.6% and 49.2% respectively the difference between which is found to be statistically significant (p = 0.04). Odds Ratio of 5.5 was noted among study subjects who were diabetic (p = 0.018). Household contacts of index patients taking CAT II were at a higher risk than that of CAT I. CONCLUSION: This study clearly shows the high prevalence of latent TB infection among household contacts of sputum positive patients receiving DOTS and so RNTCP should include them in IPT along with under 6 children. The household contacts who spend most time with the index case, who sleep close to them within 5 feet, female household contacts, students, diabetic household contacts are at a significantly higher risk than others.

When to start treatment? Dilemma illustrated by a paediatric case of extensively drug-resistant tuberculosis of the central nervous system.

An HIV-positive mother infected her daughter with extensively drug-resistant Mycobacterium tuberculosis. Despite adhering to the then current guidelines for prevention, the infant was diagnosed with extensively drug-resistant pulmonary tuberculosis at the age of 4 months and developed tuberculous meningitis. After a short delay, appropriate treatment was initiated, followed by an inhospital stay at a specialised hospital. The infant became generally well, but had delayed neurological development. Secondary hydrocephalus due to tuberculous meningitis required a ventriculoperitoneal shunt. After 2 years of microbiologically and clinically effective tuberculosis treatment and several shunt complications, the HIV-negative child died at the age of 28 months ‒ with radiological signs of a shunt infection. The reason for the fatal outcome was probably related to inadequate risk reduction of airborne mother-to-child transmission, inappropriate chemoprophylaxis and delayed initiation of adequate treatment.

Epidemiological characteristics of pulmonary tuberculosis among health-care workers in Henan, China from 2010 to 2017.

BACKGROUND: Health-care workers (HCWs) are an epidemiological group with increased exposure to tuberculosis (TB), especially at health-care facilities (HCFs) with poor TB infection control in high-TB-burden settings. China is a high-TB-burden country, and the comprehensive measures for stopping TB transmission at some HCFs were not implemented well owing to limited resources and other factors. The purpose of this study was to review risk of occupational exposure to TB among HCWs and its change trend, and identify epidemiological characteristics of pulmonary tuberculosis (PTB) among HCWs in Henan, central part of China. METHODS: A retrospective cohort study was conducted from 2010 to 2017. All HCWs and teachers in Henan were enrolled to the study as exposed group and non-exposed control group, respectively. Relative risk (RR), attributable risk (AR) and AR percent (AR%) were used to measure the association between the occupational exposure and PTB, and estimated with Poisson regression. RESULTS: The study results showed a total of 1663 cases of PTB were reported among the HCWs in Henan, accounting for 3.2‰ of all PTB cases reported in the whole population, and annual incidence rate of PTB among HCWs declined by 34% from 2010 to 2017. Over the eight years, the incidence rate of PTB among HCWs was 43.7 cases per 100,000 person-years (PYs), significantly higher than that among teachers (18.8 cases/100,000 PYs), and RR, AR and AR% were estimated to 2.3, 24.9 cases per 100,000 PYs and 57%, respectively. Among HCWs, males were more likely to suffer from PTB than females (adjusted RR: 1.3; 95%CI: 1.2-1.4), and HCWs aged under 25 years had the highest relative risk over all age groups with adjusted RR equaling to 8.3 (95%CI: 6.9-9.9) calculated with those aged 45-54 years as the reference. CONCLUSIONS: Although overall incidence rate of PTB among HCWs showed decreasing temporal trends over the period of 2010-2017, attributable risk of occupational exposure to TB among HCWs did not decrease in Henan, and TB infection at HCFs for males, young or senior HCWs, especially for young HCWs is of much concern.

Tuberculosis preventive treatment should be considered for all household contacts of pulmonary tuberculosis patients in India.

The World Health Organization (WHO) recently changed its guidance for tuberculosis (TB) preventive treatment (TPT) recommending TPT for all pulmonary TB (PTB) exposed household contacts (HHC) to prevent incident TB disease (iTBD), regardless of TB infection (TBI) status. However, this recommendation was conditional as the strength of evidence was not strong. We assessed risk factors for iTBD in recently-exposed adult and pediatric Indian HHC, to determine which HHC subgroups might benefit most from TPT. We prospectively enrolled consenting HHC of adult PTB patients in Pune and Chennai, India. They underwent clinical, microbiologic and radiologic screening for TB disease (TBD) and TBI, at enrollment, 4-6, 12 and 24 months. TBI testing was performed by tuberculin skin test (TST) and Quantiferon®- Gold-in-Tube (QGIT) assay. HHC without baseline TBD were followed for development of iTBI and iTBD. Using mixed-effect Poisson regression, we assessed baseline characteristics including TBI status, and incident TBI (iTBI) using several TST and/or QGIT cut-offs, as potential risk factors for iTBD. Of 1051 HHC enrolled, 42 (4%) with baseline TBD and 12 (1%) with no baseline TBI test available, were excluded. Of the remaining 997 HHC, 707 (71%) had baseline TBI (TST #x2265; 5 mm or QGIT #x2265; 0.35 IU/ml). Overall, 20 HHC (2%) developed iTBD (12 cases/1000 person-years, 95%CI: 8-19). HIV infection (aIRR = 29.08, 95% CI: 2.38-355.77, p = 0.01) and undernutrition (aIRR = 6.16, 95% CI: 1.89-20.03, p = 0.003) were independently associated with iTBD. iTBD was not associated with age, diabetes mellitus, smoking, alcohol, and baseline TBI, or iTBI, regardless of TST (#x2265; 5 mm, #x2265; 10 mm, #x2265; 6 mm increase) or QGIT (#x2265; 0.35 IU/ml, #x2265; 0.7 IU/ml) cut-offs. Given the high overall risk of iTBD among recently exposed HHCs, and the lack of association between TBI status and iTBD, our findings support the new WHO recommendation to offer TPT to all HHC of PTB patients residing in a high TB burden country such as India, and do not suggest any benefit of TBI testing at baseline or during follow-up to risk stratify recently-exposed HHC for TPT.

The geno-spatio analysis of Mycobacterium tuberculosis complex in hot and cold spots of Guangxi, China.

BACKGROUND: At present, there are few studies on polymorphism of Mycobacterium tuberculosis (Mtb) gene and how it affects the TB epidemic. This study aimed to document the differences of polymorphisms between tuberculosis hot and cold spot areas of Guangxi Zhuang Autonomous Region, China. METHODS: The cold and hot spot areas, each with 3 counties, had been pre-identified by TB incidence for 5 years from the surveillance database. Whole genome sequencing analysis was performed on all sputum Mtb isolates from the detected cases during January and June 2018. Single nucleotide polymorphism (SNP) of each isolate compared to the H37Rv strain were called and used for lineage and sub-lineage identification. Pairwise SNP differences between every pair of isolates were computed. Analyses of Molecular Variance (AMOVA) across counties of the same hot or cold spot area and between the two areas were performed. RESULTS: As a whole, 59.8% (57.7% sub-lineage 2.2 and 2.1% sub-lineage 2.1) and 39.8% (17.8% sub-lineage 4.4, 6.5% sub-lineage 4.2 and 15.5% sub-lineage 4.5) of the Mtb strains were Lineage 2 and Lineage 4 respectively. The percentages of sub-lineage 2.2 (Beijing family strains) are significantly higher in hot spots. Through the MDS dimension reduction, the genomic population structure in the three hot spot counties is significantly different from those three cold spot counties (T-test p = 0.05). The median of SNPs distances among Mtb isolates in cold spots was greater than that in hot spots (897 vs 746, Rank-sum test p < 0.001). Three genomic clusters, each with genomic distance ≤12 SNPs, were identified with 2, 3 and 4 consanguineous strains. Two clusters were from hot spots and one was from cold spots. CONCLUSION: Narrower genotype diversity in the hot area may indicate higher transmissibility of the Mtb strains in the area compared to those in the cold spot area.

Bacterial and host determinants of cough aerosol culture positivity in patients with drug-resistant versus drug-susceptible tuberculosis.

A burgeoning epidemic of drug-resistant tuberculosis (TB) threatens to derail global control efforts. Although the mechanisms remain poorly clarified, drug-resistant strains are widely believed to be less infectious than drug-susceptible strains. Consequently, we hypothesized that lower proportions of patients with drug-resistant TB would have culturable Mycobacterium tuberculosis from respirable, cough-generated aerosols compared to patients with drug-susceptible TB, and that multiple factors, including mycobacterial genomic variation, would predict culturable cough aerosol production. We enumerated the colony forming units in aerosols (≤10 µm) from 452 patients with TB (227 with drug resistance), compared clinical characteristics, and performed mycobacterial whole-genome sequencing, dormancy phenotyping and drug-susceptibility analyses on M. tuberculosis from sputum. After considering treatment duration, we found that almost half of the patients with drug-resistant TB were cough aerosol culture-positive. Surprisingly, neither mycobacterial genomic variants, lineage, nor dormancy status predicted cough aerosol culture positivity. However, mycobacterial sputum bacillary load and clinical characteristics, including a lower symptom score and stronger cough, were strongly predictive, thereby supporting targeted transmission-limiting interventions. Effective treatment largely abrogated cough aerosol culture positivity; however, this was not always rapid. These data question current paradigms, inform public health strategies and suggest the need to redirect TB transmission-associated research efforts toward host-pathogen interactions.

A yield and cost comparison of tuberculosis contact investigation and intensified case finding in Uganda.

INTRODUCTION: Resource constraints in Low and Middle-Income Countries (LMICs) limit tuberculosis (TB) contact investigation despite evidence its benefits could outweigh costs, with increased efficiency when compared with intensified case finding (ICF). However, there is limited data on yield and cost per TB case identified. We compared yield and cost per TB case identified for ICF and Tuberculosis-Contact Investigation (TB-CI) in Uganda. METHODS: A retrospective cohort study based on data from 12 Ugandan hospitals was done between April and September 2017. Two methods of TB case finding (i.e. ICF and TB-CI) were compared. Regarding ICF, patients either self-reported their signs and symptoms or were prompted by health care workers, while TB-CI was done by home-visiting and screening contacts of TB patients. Patients who were presumed to have tuberculosis were requested to produce a sample for examination. TB yield was defined as a ratio of diagnoses to tests, and this was computed per method of diagnosis. The cost per TB case identified (medical, personnel, transportation and training) for each diagnosis method were computed using the activity-based approach, from the health care perspective. Cost data were analyzed using Windows Excel. RESULTS: 454 index TB cases and 2,707 of their household contacts were investigated. Thirty-one per cent of contacts (840/2707) were found to be presumptive TB cases. A total of 7,685 tests were done, 6,967 for ICF and 718 for TB-CI. The yields were 18.62% (1297/6967) and 5.29% (38/718) for ICF and TB-CI, respectively. It cost US$ 120.60 to diagnose a case of TB using ICF compared to US$ 877.57 for TB-CI. CONCLUSION: The yield of TB-CI was found to be four-times lower and seven-times costlier compared to ICF. These findings suggest that ICF can improve TB case detection at a low cost, particularly in high TB prevalent settings.

Awareness and perspectives on expansion of latent TB management among public-sector physicians and medical trainees in Delhi, India.

More than one in two healthcare workers (HCWs) in developing countries have latent tuberculosis infection (LTBI), an asymptomatic condition signifying persistent tubercular infection in absence of disease. OBJECTIVE: to evaluate the physician attitude towards LTBI preventive therapy and their perspectives regarding the potential expansion of latent TB management under the RNTCP. MATERIAL AND METHODS: We conducted a cross-sectional analysis among 60 participants of a continuing medical education program during October' 2019 in a medical college in Delhi, India. RESULTS: We enrolled a total of 30 medical officers, 15 resident doctors and 15 medical interns, comprising 27 (45%) males and 33 (55%) females. Only 9 (15%) participants were aware of existing RNTCP guidelines for programmatic management of LTBI. The median (IQR) self-rated willingness of the participants in receiving treatment for LTBI after confirmation of diagnosis on a 10 point continuous rating scale was 6 (5.8). The principal reason attributed to the treatment hesitancy were concerns over drug side effects 19 (31.7%), emergence of drug resistance 11 (18.3%) and the likelihood of reinfection 4 (6.7%). Support for expansion of preventive therapy among household TB contacts was varied, with maximum (41.2%) participants wanting it only for the comorbid patients. CONCLUSION: LTBI preventive treatment is associated with considerable side effects and lack of long-term benefits by a majority of Indian physicians despite significant personal health concerns in treating pulmonary TB cases.